scholarly journals COVID-19: etiology, clinical picture, treatment

2020 ◽  
Vol 10 (3) ◽  
pp. 421-445 ◽  
Author(s):  
M. Yu. Shchelkanov ◽  
L. V. Kolobukhina ◽  
O. A. Burgasova ◽  
I. S. Kruzhkova ◽  
V. V. Maleev
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Picture ◽  
Influenza A ◽  
Artificial Respiration ◽  
Blood Oxygenation ◽  
Influenza Viruses ◽  
Type I Interferons ◽  
Type I ◽  
Similar System ◽  
History Of

Whereas the XX century marked the history of acute respiratory disease investigation as a period for generating in-depth system of combating influenza viruses (Articulavirales: Orthomyxoviridae, Alpha-/Betainfluenzavirus) (based on environmental and virological monitoring of influenza A virus in its natural reservoir — aquatic and semi-aquatic birds — to supervising epidemic influenza), a similar system is necessary to build up in the XXI century with regard to especially dangerous betacoronaviruses (Nidovirales: Coronaviridae, Betacoronavirus): Severe acute respiratory syndrome-related coronavirus (SARS-CoV) (subgenus Sarbecovirus), Severe acute respiratory syndrome-related coronavirus 2 (SARSCoV-2) (Sarbecovirus), Middle East respiratory syndrome-related coronavirus (MERS-CoV) (Merbecovirus). This became particularly evident after pandemic potential has been revealed in 2020 by the SARS-CoV-2. This review provides an insight into the historic timeline of discovering this virus, its current taxonomy, ecology, virion morphology, life cycle, molecular biology, pathogenesis and clinical picture of the etiologically related COVID-19 (Coronavirus disease 2019) as well as data available in the scientific literature on the anti-SARS-CoV-2-effectiveness of passive immunotherapy and most debated drugs used to treat COVID-19: Chloroquine, Hydroxychloroquine, Nitazoxanide, Ivermectin, Lopinavir and Ritonavir, Camostat mesilate, Remdesivir, Ribavirin, Tocilizumab, Anakinra, corticosteroids, and type I interferons. The pathogenesis of SARS-CoV-2 infection implicates decreased efficacy of artificial respiration, which, in this case might be replaced by more efficient extracorporeal membrane blood oxygenation supplemented with nitrogen oxide and/or Heliox inhalations.

IFN-κ suppresses the replication of influenza A viruses through the IFNAR-MAPK-Fos-CHD6 axis

2020 ◽  
Vol 13 (626) ◽  
pp. eaaz3381 ◽  
Author(s):  
Yongquan He ◽  
Weihui Fu ◽  
Kangli Cao ◽  
Qian He ◽  
Xiangqing Ding ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Mitogen Activated Protein Kinase ◽  
Type I Interferons ◽  
Type I ◽  
Influenza A Viruses ◽  
Human Lung Cells ◽  
Avian Influenza A Virus ◽  
Factor C

Type I interferons (IFNs) are the first line of defense against viral infection. Using a mouse model of influenza A virus infection, we found that IFN-κ was one of the earliest responding type I IFNs after infection with H9N2, a low-pathogenic avian influenza A virus, whereas this early induction did not occur upon infection with the epidemic-causing H7N9 virus. IFN-κ efficiently suppressed the replication of various influenza viruses in cultured human lung cells, and chromodomain helicase DNA binding protein 6 (CHD6) was the major effector for the antiviral activity of IFN-κ, but not for that of IFN-α or IFN-β. The induction of CHD6 required both of the type I IFN receptor subunits IFNAR1 and IFNAR2, the mitogen-activated protein kinase (MAPK) p38, and the transcription factor c-Fos but was independent of signal transducer and activator of transcription 1 (STAT1) activity. In addition, we showed that pretreatment with IFN-κ protected mice from lethal influenza viral challenge. Together, our findings identify an IFN-κ–specific pathway that constrains influenza A virus and provide evidence that IFN-κ may have potential as a preventative and therapeutic agent against influenza A virus.

scholarly journals Species-Specific Contribution of the Four C-Terminal Amino Acids of Influenza A Virus NS1 Protein to Virulence

2010 ◽  
Vol 84 (13) ◽  
pp. 6733-6747 ◽  
Author(s):  
Sébastien M. Soubies ◽  
Christelle Volmer ◽  
Guillaume Croville ◽  
Josianne Loupias ◽  
Brigitte Peralta ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Virus Replication ◽  
Influenza A ◽  
Large Scale ◽  
Influenza Viruses ◽  
Type I Interferons ◽  
Type I ◽  
Ns1 Protein ◽  
Species Specific ◽  
H7n1 Virus

ABSTRACT Large-scale sequence analyses of influenza viruses revealed that nonstructural 1 (NS1) proteins from avian influenza viruses have a conserved C-terminal ESEV amino acid motif, while NS1 proteins from typical human influenza viruses have a C-terminal RSKV motif. To test the influence of the C-terminal domains of NS1 on the virulence of an avian influenza virus, we generated a wild-type H7N1 virus with an ESEV motif and a mutant virus with an NS1 protein containing a C-terminal RSKV motif by reverse genetics. We compared the phenotypes of these viruses in vitro in human, mouse, and duck cells as well as in vivo in mice and ducks. In human cells, the human C-terminal RSKV domain increased virus replication. In contrast, the avian C-terminal ESEV motif of NS1 increased virulence in mice. We linked this increase in pathogenicity in mice to an increase in virus replication and to a more severe lung inflammation associated with a higher level of production of type I interferons. Interestingly, the human C-terminal RSKV motif of NS1 increased viral replication in ducks. H7N1 virus with a C-terminal RSKV motif replicated to higher levels in ducks and induced higher levels of Mx, a type I interferon-stimulated gene. Thus, we identify the C-terminal domain of NS1 as a species-specific virulence domain.

scholarly journals TRIM22. A Multitasking Antiviral Factor

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1864
Author(s):  
Isabel Pagani ◽  
Guido Poli ◽  
Elisa Vicenzi
Keyword(s):  
Protein Interactions ◽  
Influenza A ◽  
Direct Interaction ◽  
Type I Interferons ◽  
Viral Gene ◽  
Target Cells ◽  
Type I ◽  
Protein Protein Interactions ◽  
Viral Genomes ◽  
Dna And Rna

Viral invasion of target cells triggers an immediate intracellular host defense system aimed at preventing further propagation of the virus. Viral genomes or early products of viral replication are sensed by a number of pattern recognition receptors, leading to the synthesis and production of type I interferons (IFNs) that, in turn, activate a cascade of IFN-stimulated genes (ISGs) with antiviral functions. Among these, several members of the tripartite motif (TRIM) family are antiviral executors. This article will focus, in particular, on TRIM22 as an example of a multitarget antiviral member of the TRIM family. The antiviral activities of TRIM22 against different DNA and RNA viruses, particularly human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV), will be discussed. TRIM22 restriction of virus replication can involve either direct interaction of TRIM22 E3 ubiquitin ligase activity with viral proteins, or indirect protein–protein interactions resulting in control of viral gene transcription, but also epigenetic effects exerted at the chromatin level.

scholarly journals CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Infection ◽  
2021 ◽  
Author(s):  
Jan-Moritz Doehn ◽  
Christoph Tabeling ◽  
Robert Biesen ◽  
Jacopo Saccomanno ◽  
Elena Madlung ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Clinical Studies ◽  
Viral Infections ◽  
Severe Disease ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Expression Levels

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

scholarly journals IFITM3 and type I interferons are important for the control of influenza A virus replication in murine macrophages

Virology ◽  
2020 ◽  
Vol 540 ◽  
pp. 17-22 ◽  
Author(s):  
Sarah L. Londrigan ◽  
Linda M. Wakim ◽  
Jeffrey Smith ◽  
Anne J. Haverkate ◽  
Andrew G. Brooks ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Virus Replication ◽  
Influenza A ◽  
Type I Interferons ◽  
Type I ◽  
Murine Macrophages

scholarly journals Detection of severe acute respiratory syndrome coronavirus 2 and influenza viruses based on CRISPR-Cas12a

2020 ◽  
pp. 153537022096379
Author(s):  
Oraphan Mayuramart ◽  
Pattaraporn Nimsamer ◽  
Somruthai Rattanaburi ◽  
Naphat Chantaravisoot ◽  
Kritsada Khongnomnan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Influenza A ◽  
Limit Of Detection ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza Virus A ◽  
B Virus

Due to the common symptoms of COVID-19, patients are similar to influenza-like illness. Therefore, the detection method would be crucial to discriminate between SARS-CoV-2 and influenza virus-infected patients. In this study, CRISPR-Cas12a-based detection was applied for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus which would be a practical and attractive application for screening of patients with COVID-19 and influenza in areas with limited resources. The limit of detection for SARS-CoV-2, influenza A, and influenza B detection was 10, 103, and 103 copies/reaction, respectively. Moreover, the assays yielded no cross-reactivity against other respiratory viruses. The results revealed that the detection of influenza virus and SARS-CoV-2 by using RT-RPA and CRISPR-Cas12a technology reaches 96.23% sensitivity and 100% specificity for SARS-CoV-2 detection. The sensitivity for influenza virus A and B detections was 85.07% and 94.87%, respectively. In addition, the specificity for influenza virus A and B detections was approximately 96%. In conclusion, the RT-RPA with CRISPR-Cas12a assay was an effective method for the screening of influenza viruses and SARS-CoV-2 which could be applied to detect other infectious diseases in the future.

The influenza virus PB1-F2 protein has interferon antagonistic activity

2011 ◽  
Vol 392 (12) ◽  
pp. 1135-1144 ◽  
Author(s):  
Sabine E. Dudek ◽  
Ludmilla Wixler ◽  
Carolin Nordhoff ◽  
Alexandra Nordmann ◽  
Darisuren Anhlan ◽  
...  
Keyword(s):  
Influenza A ◽  
Molecular Mechanisms ◽  
Nonstructural Protein ◽  
Gene Segment ◽  
Antagonistic Activity ◽  
Influenza Viruses ◽  
Type I ◽  
Influenza A Viruses ◽  
Reading Frame

Abstract PB1-F2 is a nonstructural protein of influenza viruses encoded by the PB1 gene segment from a +1 open reading frame. It has been shown that PB1-F2 contributes to viral pathogenicity, although the underlying mechanisms are still unclear. Induction of type I interferon (IFN) and the innate immune response are the first line of defense against viral infection. Here we show that influenza A viruses (IAVs) lacking the PB1-F2 protein induce an enhanced expression of IFN-β and IFN-stimulated genes in infected epithelial cells. Studying molecular mechanisms underlying the PB1-F2-mediated IFN antagonistic activity showed that PB1-F2 interferes with the RIG-I/MAVS protein complex thereby inhibiting the activation of the downstream transcription factor IFN regulatory factor 3. These findings were also reflected in in vivo studies demonstrating that infection with PR8 wild-type (wt) virus resulted in higher lung titers and a more severe onset of disease compared with infection with its PB1-F2-deficient counterpart. Accordingly, a much more pronounced infiltration of lungs with immune cells was detected in mice infected with the PB1-F2 wt virus. In summary, we demonstrate that the PB1-F2 protein of IAVs exhibits a type I IFN-antagonistic function by interfering with the RIG-I/MAVS complex, which contributes to an enhanced pathogenicity in vivo.

scholarly journals Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raveen Rathnasinghe ◽  
Mirella Salvatore ◽  
Hongyong Zheng ◽  
Sonia Jangra ◽  
Thomas Kehrer ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Type I ◽  
Respiratory Pathogens ◽  
Structural Protein ◽  
Human Influenza Virus

AbstractThe influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex

2009 ◽  
Vol 284 (24) ◽  
pp. 16202-16209 ◽  
Author(s):  
Kam-Leung Siu ◽  
Kin-Hang Kok ◽  
Ming-Him James Ng ◽  
Vincent K. M. Poon ◽  
Kwok-Yung Yuen ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Transcriptional Activity ◽  
Type I Interferons ◽  
M Protein ◽  
Type I ◽  
Sars Coronavirus ◽  
Front Line ◽  
Highly Pathogenic ◽  
Double Stranded Rna ◽  
Multiple Levels

Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in humans and evades innate immunity at multiple levels. It has evolved various strategies to counteract the production and action of type I interferons, which mobilize the front-line defense against viral infection. In this study we demonstrate that SARS coronavirus M protein inhibits gene transcription of type I interferons. M protein potently antagonizes the activation of interferon-stimulated response element-dependent transcription by double-stranded RNA, RIG-I, MDA5, TBK1, IKKϵ, and virus-induced signaling adaptor (VISA) but has no influence on the transcriptional activity of this element when IRF3 or IRF7 is overexpressed. M protein physically associates with RIG-I, TBK1, IKKϵ, and TRAF3 and likely sequesters some of them in membrane-associated cytoplasmic compartments. Consequently, the expression of M protein prevents the formation of TRAF3·TANK·TBK1/IKKϵ complex and thereby inhibits TBK1/IKKϵ-dependent activation of IRF3/IRF7 transcription factors. Taken together, our findings reveal a new mechanism by which SARS coronavirus circumvents the production of type I interferons.

scholarly journals The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways

2011 ◽  
Vol 92 (9) ◽  
pp. 2093-2104 ◽  
Author(s):  
Jennifer R. Tisoncik ◽  
Rosalind Billharz ◽  
Svetlana Burmakina ◽  
Sarah E. Belisle ◽  
Sean C. Proll ◽  
...  
Keyword(s):  
Gene Expression ◽  
Antigen Presentation ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Mutant Virus ◽  
Type I ◽  
Ns1 Protein ◽  
Effector Domain ◽  
Regulated Gene Expression

The NS1 protein of influenza virus counters host antiviral defences primarily by antagonizing the type I interferon (IFN) response. Both the N-terminal dsRNA-binding domain and the C-terminal effector domain are required for optimal suppression of host responses during infection. To better understand the regulatory role of the NS1 effector domain, we used an NS1-truncated mutant virus derived from human H1N1 influenza isolate A/Texas/36/91 (Tx/91) and assessed global transcriptional profiles from two independent human lung cell-culture models. Relative to the wild-type Tx/91-induced gene expression, the NS1 mutant virus induced enhanced expression of innate immune genes, specifically NF-κB signalling-pathway genes and IFN-α and -β target genes. We queried an experimentally derived IFN gene set to gauge the proportion of IFN-responsive genes that are suppressed specifically by NS1. We show that the C-terminally truncated NS1 mutant virus is less efficient at suppressing IFN-regulated gene expression associated with activation of antigen-presentation and immune-proteasome pathways. This is the first report integrating genomic analysis from two independent human culture systems, including primary lung cells, using genetically similar H1N1 influenza viruses that differ only in the length of the NS1 protein.

Sign in / Sign up

Export Citation Format

Share Document